Applicability of Computational Language Technologies to Identify Independent Protein Folding Domains in Human Proteins

计算语言技术在识别人类蛋白质中独立蛋白质折叠域的应用

• 批准号: 0204078
• 负责人: Judith Klein
• 金额: $ 9.96万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-15 至 2002-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0204078&HistoricalAwards=false
• 关键词: Applicability; Computational; Language; Technologies; Identify

Several lines of evidence suggest that there exists a strong analogy between natural languages and biological sequences, i.e. there appear to be organism-specific words, phrases and paragraphs in the collective of proteins encoded by the genomes of fully sequenced organisms. It is proposed that the biological analogy of meaning in a natural text is the ability of a protein sequence to fold into its functional three-dimensional fold. In natural languages, frequent words carry little meaning, while rare words often allow identification of the topic of a particular text. The hypothesis predicts, therefore, that rare stretches of amino acids indicate the location of folding initiators. The distribution of global properties along the sequence of lysozyme, a model protein for protein folding studies, indicated that features in these properties can be recognized when inverse frequencies of amino acid n-grams were plotted, supporting the analogy to natural languages. In the next 12 months the focus will be on studying the distribution of rare n-grams in the human genome. If a correlation between folding domains and distribution of rare n-grams can be established, this would (i) provide compelling support for the hypothesis and (ii) shed light on one of the major unsolved questions in biology today, the mechanism by which functional three-dimensional structures are formed from a one-dimensional sequence of amino acids.

一些证据表明，自然语言和生物序列之间存在很强的相似性，即在完全测序的生物体基因组编码的蛋白质集合中似乎存在生物体特有的单词、短语和段落。 有人提出，在一个自然的文本意义的生物类比是一个蛋白质序列折叠成其功能的三维折叠的能力。 在自然语言中，频繁出现的单词没有什么意义，而罕见的单词通常可以识别特定文本的主题。 因此，该假说预测，罕见的氨基酸片段指示折叠起始子的位置。 全局属性沿着溶菌酶，蛋白质折叠研究的模型蛋白质的序列的分布表明，这些属性中的功能可以被识别时，氨基酸的n-gram的频率倒数绘制，支持自然语言的类比。 在接下来的12个月里，重点将放在研究人类基因组中罕见的n-gram的分布上。 如果折叠结构域和罕见的n-grams分布之间的相关性可以建立，这将（i）为假设提供令人信服的支持，（ii）阐明当今生物学中未解决的主要问题之一，功能性三维结构由一维氨基酸序列形成的机制。